West Nile virus (“WNV”) is a member of the Flaviviridae family, genus Flavivirus. Flaviviruses are small spherical enveloped positive-strand RNA viruses. The Flavivirus genus comprises more than 60 highly related viruses including several human pathogens such as inter alia yellow fever virus, Japanese encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, tick-borne encephalitis virus, and dengue virus.
WNV was initially isolated in 1937 in the West Nile region of Uganda but has now an almost worldwide distribution including parts of Africa, Asia, Australia, Europe and, most recently, North America. WNV was first diagnosed in the New York area in 1999 and has continued to spread rapidly across North America causing infections in persons in over 40 different states reaching as far as California.
WNV is mainly transmitted to man by mosquitoes but occasionally transmission has been linked to blood transfusion and organ transplantation. WNV infections generally have mild symptoms, which generally last three to six days, varying from a fever of sudden onset, headache, tremors, skin rash to swollen lymph glands. However, in 30% of the cases, particularly in elderly and immunocompromised patients, the disease progresses to a more severe state (e.g., encephalitis or aseptic meningitis), which can lead to death. By 2002, human mortality increased to over 150 cases. Besides infecting humans, WNV is also known to infect horses and several bird species and can cause severe illness and death in those species.
The two main strategies for preventing WNV infections are a) controlling the spread of WNV by spraying large areas with insecticides to kill mosquito vectors and b) reducing the contact between humans and mosquitoes by using personal protection such as anti-insect repellents. Unfortunately, these strategies are however highly inefficacious. Furthermore, there are concerns regarding the toxic effects of insecticides. Moreover, spraying requires repeated applications and is considered to be unreliable, as it does not provide complete coverage of mosquito breeding areas or eradication of mosquitoes.
There is no specific treatment of WNV infection. Treatment has only been supportive, since there are no available anti-viral or other drugs with proven efficacy. The most promising potential treatment options currently available for humans include the anti-viral compounds ribavirin and interferon-alpha2b (Anderson and Rahal, 2002), and human anti-WNV immunoglobulins (Ben Nathan et al., 2003). A disadvantage associated with ribavirin and interferon alpha2b are their significant toxicities. A disadvantage of anti-WNV immunoglobulins is that they are not available in sufficient amounts and are too expensive. In addition, the possibility of contamination by known or unknown pathogens is an additional concern associated with anti-WNV immunoglobulins. Furthermore, in PCT International Application WO 02/072036, the contents of which are incorporated by this reference, it has been suggested that the WNV F protein may be used to prepare murine anti-WNV monoclonal antibodies. However, murine antibodies, in naked or immunoconjugated format, are limited for their use in vivo due to problems associated with administration of murine antibodies to humans, such as short serum half life, an inability to trigger certain human effector functions and elicitation of an unwanted dramatic immune response against the murine antibody in a human. Accordingly, an urgent need exists for a medicament suitable for detection, prevention and/or treatment of WNV infections.